1. Field of the Invention
This invention relates to a biochemical process of separating a material from a fluid medium. The invention extends to a carrier medium for removing the material from the fluid medium and to a bioreactor and an affinity column containing such a carrier medium.
2. Description of the Related Art
The invention has particular reference to the production of various kinds of biological materials which are produced by animal or vegetable cells. Examples of such materials are viral proteins, cytokines, hormones, enzymes, monoclonal antibodies, viral and bacterial vaccines, pharmaceuticals, and cell components, such as chromosomes and cellular organelles. Other examples include whole cells, for example, for artificial skin transplants or grafts of liver, pancreatic, renal or spleen cells.
The invention is also relevant to biological materials which have been obtained by means other than biological processing, for example by mechanical crushing of biological tissue, and to materials, such as alcohols and ammonia, produced by a biological process and which need to be separated from the biological production medium. For example, certain yeasts produce alcohol which if not removed builds up to a concentration toxic to the yeast. Additionally, the invention is relevant to biochemical processes for the depollution or purification of a fluid medium.
Because of the important and increasing demand in human and veterinary medicine for biological materials which are produced by animal cells the invention will however be described hereinafter with particular reference to the production of such materials.
According to classical methods, biological materials are produced from animal cells by a fermentation process in a culture vessel from which the desired product must be separated and purified. The desired product is often highly diluted and present in only small proportions in the culture medium which also contains many contaminants. Because of the dilution, very large quantities of the culture medium need to be processed and concentrated before purification takes place. Because of the contamination, the product is very difficult to separate, and in classical methods, many separation stages are required. This is very time consuming and therefore expensive. Moreover, such processes must be performed batch-wise. Cells are grown for a period of time in a culture vessel (bioreactor) containing nutritive medium and the culture medium is then processed to remove and purify the desired product. Procedures for such purification often include separation of the cells and processing of the acellular culture medium in several purification steps which take advantage of biochemical or biophysical characteristics of the desired product in order to separate it progressively from the contaminating material. A separation step may for example be performed by passing the culture medium through a column containing a porous matrix constituted by a bed of particles such as balls of agarose or polyacrylamide which have been treated to have affinity for the desired product, and removing the product from the carrier particles e.g. by exposing the carrier particles to a medium which has a pH different from that of the culture medium. As an example, an antigen may be separated from a culture medium by coating the carrier particles with an antibody for that antigen. Since such multistep and batch-wise processing requires storage of the biological medium to be purified, exposing it to the risk of degradation, and requires adaptation of the individual reactants at each successive step, it is by its very nature inefficient and expensive.